The present study aimed to explore the characteristic
ions distinguishing different Barcelona stages in patients with hepatitis B virus (HBV)-associated
hepatocellular carcinoma (HCC) using the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) platform, and to evaluate their value in diagnosing and monitoring the progress of HCC. The serum was sampled from 20 healthy volunteers, 20 patients with HBV-induced
cirrhosis and 75 patients with HBV-associated HCC of different BCLC stages. Samples were all examined using UPLC-MS. Principal components analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA) model were constructed to determine potential
biomarkers. Then, the independent sample-nonparametric test was used to perform the final screening for ion identification. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of these
ions. Serum metabolomic PCA and OPLS-DA models were established to diagnose different BCLC stages of HCC associated with HBV, with OPLS-DA model parameters (R2X=67.2%, R2Y=82%, Q2Y=61.1%). A total of 20 metabolites with statistically significant differences among groups were identified, primarily including
amino acids,
bile acid,
fatty acid and phosphatidate. The area under the curve (AUC) of LysoPC [18:2 (9Z,12Z)], LysoPC (P-16:0),
asparaginyl-proline and
vaccenic acid in the comparison between HCC and
cirrhosis were all increased compared with that of AFP, indicating a more improved diagnosis ability. Furthermore, the AUC of L-aspartyl-4-phosphate and LysoPC [20:5 (5Z,8Z,11Z,14Z,17Z)] in the stage A vs. B comparison were increased compared with that of AFP, but were decreased in the comparison between stage B and C. The present study succeeded in screening metabolic
ions that reflect the progress of HCC with high diagnostic value. Thus, the identified
ions may serve a role in clinically diagnosing HBV-associated HCC and monitoring the development of the disease.